Insulin resistance in patients with polcystic ovary syndrome is associated with elevated plasma homocysteine

Morey Schachter*, Arieh Raziel, Shevach Friedler, Deborah Strassburger, Orna Bern, Raphael Ron-El

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Elevated levels of plasma homocysteine have recently been implicated as a significant risk factor for cardiovascular disease, pre-eclampsia, and recurrent pregnancy loss, and have been found to be associated with insulin resistance in a number of clinical situations. We examined the relationship between plasma homocysteine and insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods: A total of 155 infertile patients with PCOS as defined by clinical, biochemical and ultrasound criteria were screened for insulin resistance utilizing single-sample fasting insulin and glucose measurement, calculated by glucose:insulin ratio or homeostasis model assessment (HOMA) index. Total plasma homocysteine was measured by fluorescence polarization immunoassay. One hundred normo-ovulatory women with normal ovaries being treated for other infertility diagnoses served as a control group. Results: Insulin resistance was found in the majority of PCOS patients: -53.5% (83/155), 60.6% (94/155) and 65.8% (102/155), when defined by fasting insulin, glucose:insulin ratio, or logHOMA respectively. Mean plasma homocysteine in the PCOS group was significantly higher than in the normal ovary group (11.5 ± 7.4 versus 7.4 ± 2.1 μmol/l, P < 0.001). Insulin-resistant PCOS patients had significantly higher plasma homocysteine (12.4 ± 8.4 μmol/l) than non-insulin-resistant PCOS patients (9.6 ± 4.4 μmol/l) regardless of body mass index (P = 0.003 by groups, P = 0.005 by correlation of single samples). Thirty-four per cent (53/155) of the PCO patients had homocysteine values >95th percentile of the controls (11.0 μmol/l, P < 0.0001). Statistically significant correlations were found between all insulin resistance indices and homocysteine levels. Multiple logistic regression defined insulin resistance as the major factor examined that influenced homocysteine levels. Conclusions: Insulin resistance and hyperinsulinaemia in patients with PCOS is associated with elevated plasma homocysteine, regardless of body weight. This finding may have important implications in the short term regarding reproductive performance, and in the long term regarding cardiovascular complications associated with insulin-resistant PCOS.

Original languageEnglish
Pages (from-to)721-727
Number of pages7
JournalHuman Reproduction
Issue number4
StatePublished - 1 Apr 2003


  • Homocysteine
  • Insulin resistance
  • Metabolic syndrome
  • Polycystic ovary syndrome


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